A biosensor may be denoted as a device which may be used for the detection of an analyte that combines a biological component with a physicochemical or physical detector component.
For instance, a biosensor may be based on the phenomenon that capture molecules immobilized on a surface of a biosensor may selectively hybridize with target molecules in a fluidic sample, for instance when an antibody-binding fragment of an antibody or the sequence of a DNA single strand as a capture molecule fits to a corresponding sequence or structure of a target molecule. When such hybridization or sensor events occur at the sensor surface, this may change the electrical properties of the surface and the volume directly above the surface which can be detected as the sensor event.
Many suitable specific binding pair candidates are known per se, which are typically based on a lock-and-key type interaction between a receptor molecule and a molecule, e.g. a drug. This makes a sensing apparatus such as an assay-based apparatus particularly suitable to determine the presence or absence of specific proteins and other biological compounds such as DNA, RNA, hormones, metabolites, drugs and so on, or to determine the activity and function of active and catalytic biomolecules such as proteins, peptides, prions, enzymes, aptamers, ribozymes and deoxyribozymes. For instance, immunoassays are already used to determine the specific amount of specific proteins in body fluids to aid further diagnosis and treatment.
Due to advances in semiconductor technology, it has become feasible to detect single capture events on a sensing surface of such sensors. An example of such a sensor is disclosed in PCT patent application WO 2009/047703, in which a capture molecule forms an insulating layer of a capacitor, with the plates of the capacitor formed by a conductive sensing surface and a fluid sample respectively. A capture event causes a change in the dielectric constant of the insulating layer including the volume directly above the sensor surface in which a capture event takes place, which affects the capacity of the capacitor. The change in capacitance can be measured, e.g. as a bias on a current through a transistor, as is the case in this application.
An alternative arrangement is disclosed in PCT patent application WO 2008/132656, in which an extended gate field effect transistor is disclosed with capture molecules on the surface of the extended gate, such that the gate potential of the transistor can be altered by capture events.
Another type of biosensor that has been gaining considerable attention is an assay-type biosensor in which antibodies are bound to magnetic beads, which are attracted to a sensing surface carrying further antibodies by a magnetic force, with the analyte of interest binding the magnetic beads to the sensing surface by forming a binding pair with the antibodies and the further antibodies. Examples of such assays are for instance given in PCT patent application WO 2007/060601.
A problem associated with such type of sensors is that contamination of the sensing surface with non-specific binding events also affects a sensing event, i.e. introduces noise to the measurement, thus decreasing the reliability of the sensor reading. This is detrimental to any type of sensor that has a sensing surface adapted to measure the formation of specific binding pairs, and in particular to the type of sensor such as disclosed in WO 2009/047703, because for such sensors a single non-specific binding event is likely to introduce noise at a magnitude comparable to the magnitude of the signal generated by the binding pair.